An autonomic nervous system is formed of a sympathetic nervous system and a parasympathetic nervous system, and involuntarily controls actions of internal organs, blood vessels and the like.
For example, when an impulse is transmitted through the sympathetic nerve to a cardiovascular system (such as heart and blood vessels), a blood pressure, pulse and the like are adjusted by increasing a heart rate and constricting the blood vessels. In this case, in the sympathetic nerve, a substance (neurotransmitter) called adrenaline or noradrenaline is secreted from a terminal (synapse) of a nerve cell. These neurotransmitter act on specific receptors present in the heart or vascular smooth muscles, by which impulses are transmitted to the heart and blood vessels, to thereby control the actions thereof.
Herein, the receptor on which adrenaline and noradrenaline can act is called an adrenergic receptor, and classified into two types: α receptor and β receptor. The α receptor is further classified into α1 receptor and α2 receptor, while the β receptor is further classified into β1 receptor and β2 receptor.
Briefly, the α receptor is associated with functions including vasoconstriction, and the β receptor is associated with functions including increase in the heart rate. It should be noted that the α1 adrenergic receptor is known to be present in the vascular smooth muscle, prostatic smooth muscle and the like, and is associated with constrictions thereof.
An antagonist of the adrenergic receptor is capable of acting on the above-mentioned α receptor or β receptor competitively or noncompetitively with the neurotransmitters (such as adrenaline and noradrenaline), to block a transmission of an impulse by the neurotransmitter in the sympathetic nerve.
Therefore, for example, when the antagonist capable of acting on the α1 adrenergic receptor (hereinafter, referred to as “α1 adrenergic receptor antagonist”) acts on the α1 adrenergic receptor present in the vascular smooth muscle, it is possible to make the vascular smooth muscle relaxed to dilate the blood vessel. As a result, a vascular resistance is reduced which in turn reduces the blood pressure (in other words, the antagonist is capable of functioning as a hypotensive drug).
Examples of the conventional α1 adrenergic receptor antagonist having such a function include phentolamine, phenoxybenzamine and prazosin, and an α1 adrenergic receptor antagonistic agent including these α1 adrenergic receptor antagonists has been used mainly as an antihypertensive drug, or as a drug for prostatic hypertrophy or the like (see nonpatent document 1). It should be noted that the prostatic hypertrophy is characterized as a benign tumor of a prostate grand with a high prevalence in elderly men, which is likely to become a factor of dysuria. The α1 adrenergic receptor antagonist may release the constriction of a urethra caused by prostatic hypertrophy and thus improve urination, by acting on the α1 adrenergic receptor present in the prostatic smooth muscle.
However, the conventional α1 adrenergic receptor antagonistic agents are often accompanied by various side effects (e.g., orthostatic hypotension and vertigo), and thus it has been desired that a novel α1 adrenergic receptor antagonistic agent be further developed.
The present invention is made with the view toward solving the above-mentioned current conditions, and provides a novel compound, an α1 adrenergic receptor antagonistic agent and a composition, which are capable of exerting a therapeutic effect in treatment of hypertension as well as treatment of prostatic hypertrophy and the like.
Nonpatent Document 1: “Goodman & Gilman's The Pharmacological Basis of Therapeutics 10th edition” (Vol. 1), translation supervised by Shuuji Takaori, Hideomi Fukuda and Akinori Akaike, Hirokawa Book Co., p 308-316